U.S. Pat. No. 4,743,685 describes 2-oxo-1-[[(substituted sulfonyl)-amino]carbonyl]azetidines having antibacterial activity. These azetidines can be characterized by the general formula ##STR2## wherein A.sub.1 represents various amino groups and substituted N-heterocyclic groups. Preferred compounds, as disclosed by the application, are [[[[[(1,4-dihydro-5-hydroxy-4-oxo-2-pyridinyl)carbonyl]amino]-2-oxo-imidaz olidinyl]sulfonyl]-amino]carbonyl-2-oxo-azetidines having the formula ##STR3##
Several processes for preparing the above compounds are described. In one process, protected .beta.-lactams of the formula ##STR4## (wherein Prot is an amino protecting group such as benzyloxycarbonyl, t-butoxycarbonyl, trityl and the like) are reacted with an isocyanate of the formula EQU O.dbd.C.dbd.N--SO.sub.2 --Y, (iv)
wherein Y is a leaving group such as chlorine, to provide intermediates of the formula ##STR5##
The Y leaving group can be displaced by reaction of a compound of formula (v) with the nucleophile of the formula ##STR6## for example, in the case where A.sub.1 of formula (i) is ##STR7## typically in the presence of a base, to provide intermediates of the formula ##STR8##
Deprotection and acylation are described to couple the desired R.sub.1 moiety at the 3-amino site.
Alternatively, .beta.-lactams other than compound (iii) are described as suitable for coupling with the isocyanate (iv) and acylation may be carried out at other points in the process.
To prepare the compound of formula (vi), a compound of the formula ##STR9## is provided with hydroxyl group protection followed by carboxyl activation and reacted with a compound of the formula ##STR10##
The so-formed compound (vi) is thereafter temporarily protected for coupling with compound (v) and then must be reprotected for the acylation to add R.sub.1.
In scaling up this process for the purpose of manufacturing the compounds of formula (i), the numerous protection, deprotection and reprotection steps necessary in the described process render it costly and less efficient than preferred. Additionally, it has been found that because of the extremely water soluble nature of compound (ix) (and other H--A.sub.1 --NH.sub.2 intermediates), its isolation for use in the described process is very difficult.
A more efficient process for making the compounds of formula (i) has been sought.